from Wiktionary, Creative Commons Attribution/Share-Alike License
- What are you doing?; what is happening?
- How are you?; how are you feeling?
- What’s the matter?
- A casual greeting with a meaning similar to how are you? or nice to meet you.
Made popular by the cartoon character Bugs Bunny who used it as early as 1940 as part of his catch phrase “What’s up Doc?” (where each word was pronounced distinctly). (Wiktionary)